Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy.

Autor: Rajabian N; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Choudhury D; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Ikhapoh I; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Saha S; Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Kalyankar AS; Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Mehrotra P; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Shahini A; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Breed K; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA., Andreadis ST; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York, USA.; Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, New York, USA.; Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Amherst, New York, USA.; Cell, Gene and Tissue Engineering (CGTE) Center, School of Engineering and Applied Sciences, University at Buffalo, State University of New York, Amherst, New York, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2023 Mar; Vol. 22 (3), pp. e13764. Date of Electronic Publication: 2023 Jan 10.
DOI: 10.1111/acel.13764
Abstrakt: Cellular senescence leads to the depletion of myogenic progenitors and decreased regenerative capacity. We show that the small molecule 2,6-disubstituted purine, reversine, can improve some well-known hallmarks of cellular aging in senescent myoblast cells. Reversine reactivated autophagy and insulin signaling pathway via upregulation of Adenosine Monophosphate-activated protein kinase (AMPK) and Akt2, restoring insulin sensitivity and glucose uptake in senescent cells. Reversine also restored the loss of connectivity of glycolysis to the TCA cycle, thus restoring dysfunctional mitochondria and the impaired myogenic differentiation potential of senescent myoblasts. Altogether, our data suggest that cellular senescence can be reversed by treatment with a single small molecule without employing genetic reprogramming technologies.
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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